N-allylnormorphine and processes for its production



Patented Dec. 12, 1944 Y Y UNITED STATES PATENT OFFICE p N -ALLYLNORMORPHIN E AND PROCESSES FOR ITS PRODUCTION John Weijlard, Westfield, N. J., and Arthur E. Erickson, Brooklyn, N. Y., assignors to Merck & 530., Inc., Rahway, N. J a corporation of New ersey I No Drawing. Application December 6, 1941,

Serial No. 421,962

Claims. (01. ace-285) This invention relates to N-allylnormorphine, tion, and cooled in the icebox overnight, The

and to processes for producing the same. white crystals are collected, washed with some The only process for producing N-allylnormorether, and dried in vacuo; melting point 208- phine previously described in the literature is that 209 C.

of McCawley, Hart and Marsh, Jr. Am.Chem. Soc., 5 Anal. calcd. for C19H2103N: C, 73.26; H, 6.80;

63, 314 (1941). However, we have not succeeded N, 4.50. Found: C, 73.19; H, 7.18; N, 4.54.

in preparing N-allylnormorphine by that process, I In the above example, allyl chloride may beand have found no evidence of reaction between used in place of allyl bromide.

N -normorphine and allyl bromide under the con- Thebase is soluble in dilute alkali and gives a ditions described by McCawley et al., the normorpositive FeCls test, indicating a free phenolic phine being recovered substantially quantitatively group. It is soluble in chloroform, alcohol, and

unchanged. acetone, and sparingly soluble in ether or water. We have now succeeded in preparing N-allyl- Salts of the free base may be prepared by treatnormorphine and its salts, such as the hydroment thereof with corresponding acids; Thus,

bromide, for example, in analytically pure form, for the preparation of the hydrobromide, for inand have found that their properties are entirely stance, the free base is dissolved in ethanol, and

different than had been reported previously. The a slight excess of alcoholic hydrobromic acid is analytically pure N-allylnormorphine prepared added; the hydrobromide crystallizes out rapidly accordingly'to our invention occurs in the form of on scratching. The crystals are collected, washed white crystals of melting point 208-209 C. with cold alcohol, and dried in vacuo; melting We have confirmed the structure of our N -allylpoint 258-259 C. normorphine by methylating the compound to the Modifications may be made in carrying out the corresponding N-allyl norcodeine, and comparing present invention, but itis to be understood that that compound with N-allyl-norcodeine prepared we are to be limited only by the appended claims. according to von Braun [Berichte 49, 977, (1916) We claim:

A mixed melting point determination of samples 1. A substantially pure substance selected from of our N-allylnorcodeine and the product prethe group consisting of N-allylnormorphine, a

pared according to von Braun showed no depreswhite crystalline solid of formula C19H2103N, meltsion. il'lg at approximately 208209 0., and salts there- The following example illustrates a method of of.

carrying out the present invention, butit is to be 2. Substantially pure N-allylnormorphine, a

understood that this example is by way of illuswhite crystalline substance of formula C19H2l03N, tration, and not of limitation. and melting at approximately 208-209 C.

e 3. Substantially pure N-allylnormorphine hy- Exampze 4 drobromide, a crystallinesubstance melting at Thirty-five gms. of normorphine (2 mol. equivapproxlmetely 258459 alents) and 7.95 gms. of allyl bromide (1 mol. Process empnsmg reactmg normorequivalent) in 350 cc. of chloroform are heated in Phine with a Substance Selected from the group a sealed tube at 110 C. for three and one-half consisting of allyl bromide and allyl chloride in hours. The reaction mixture is filtered, and the 40 an Organic solvent and at a temperature about solid residue washed with chloroform. From this and recovering substantially pure residue of normorphine hydrobromide, about 13 ally o mo p i gms. of normorphine are recovered by dissolving 5- The P ss comprising reacting ppr xiin water and precipitating the base with amat y 2 mol. equivalents of. 0r 0rDhine with monia water at a pH of 8. approximately 1 mol. equivalent of a substance The chloroform solution is evaporated to dryselected from the group consisting of allyl broness in vacuo, and the residue triturated with mide and allyl chloride, in an organic solvent, and

cc. of ether, cooled in an ice bath for two hours, ata temperature of about C., and recovering:

and filtered. The crude N-allyl-normorphine is substantially pure N-allylnormorphine. extracted for 15 hours in a Soxhlet extractor with 50 JOHN WEIJLARD. anhydrous ether. The ether extract is concen- ARTHUR E. ERICKSON. trated in absence of air to incipient crystalliza- 

